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gut metabolome

Xiaojing Liu, Iris L Romero, Lacey M Litchfield, Ernst Lengyel, Jason W Locasale
Repurposing metformin for cancer therapy is attractive due to its safety profile, epidemiological evidence, and encouraging data from human clinical trials. Although it is known to systemically affect glucose metabolism in liver, muscle, gut, and other tissues, the molecular determinants that predict a patient response in cancer remain unknown. Here, we carry out an integrative metabolomics analysis of metformin action in ovarian cancer. Metformin accumulated in patient biopsies, and pathways involving nucleotide metabolism, redox, and energy status, all related to mitochondrial metabolism, were affected in treated tumors...
October 12, 2016: Cell Metabolism
Joshua M A Stough, Stephen P Dearth, Joshua E Denny, Gary R LeCleir, Nathan W Schmidt, Shawn R Campagna, Steven W Wilhelm
C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome...
2016: Frontiers in Microbiology
Nir Friedman, Eran Shriker, Ben Gold, Thomer Durman, Raphy Zarecki, Eytan Ruppin, Itzhak Mizrahi
Dietary changes are known to affect gut community structure, but questions remain about the mechanisms by which diet induces shifts in microbiome membership. Here we addressed these questions in the rumen microbiome ecosystem - a complex microbial community that resides in the upper digestive tract of ruminant animals and is responsible for the degradation of the ingested plant material. Our dietary intervention experiments revealed that diet affects the most abundant taxa within the microbiome and that a specific group of methanogenic archaea of the order Methanomicrobiales is highly sensitive to its changes...
October 1, 2016: Environmental Microbiology
Ishfaq Ahmed, Badal C Roy, Salman A Khan, Seth Septer, Shahid Umar
Inflammatory Bowel Disease (IBD) is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn's Disease (CD) or Ulcerative Colitis (UC), two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome) and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing...
June 15, 2016: Microorganisms
Juscelino Tovar, Vanessa D de Mello, Anne Nilsson, Maria Johansson, Jussi Paananen, Marko Lehtonen, Kati Hanhineva, Inger Björck
SCOPE: MFD, a diet based on multiple functional concepts and ingredients with antiinflammatory activity, was previously shown to improve different cardiometabolic risk-associated markers in healthy subjects. Here, we assessed the impact of MFD on plasma metabolome and explored associations of the differential metabolites with clinical parameters, searching for metabolic determinants related to the effects of MFD. METHODS AND RESULTS: Forty-four overweight healthy volunteers completed a randomized crossover intervention comparing MFD with a control diet devoid of the active components of MFD...
September 27, 2016: Molecular Nutrition & Food Research
Natalia Zeber-Lubecka, Maria Kulecka, Filip Ambrozkiewicz, Agnieszka Paziewska, Krzysztof Goryca, Jakub Karczmarski, Tymon Rubel, Wojciech Wojtowicz, Piotr Mlynarz, Lukasz Marczak, Roman Tomecki, Michal Mikula, Jerzy Ostrowski
Irritable bowel syndrome (IBS) is a chronic functional disorder and its development may be linked, directly and indirectly, to intestinal dysbiosis. Here we investigated the interactions between IBS symptoms and the gut microbiome, including the relation to rifaximin (1200 mg daily; 11.2 g per a treatment). We recruited 72 patients, including 31 with IBS-D (diarrhea), 11 with IBS-C (constipation), and 30 with IBS-M (mixed constipation and diarrhea) and 30 healthy controls (HCs). Of them, 68%, 64%, and 53% patients with IBS-D, IBS-C, and IBS-M, respectively, achieved 10-12 week-term improvement after the rifaximin treatment...
September 2, 2016: Gut Microbes
Richard D Beger, Warwick Dunn, Michael A Schmidt, Steven S Gross, Jennifer A Kirwan, Marta Cascante, Lorraine Brennan, David S Wishart, Matej Oresic, Thomas Hankemeier, David I Broadhurst, Andrew N Lane, Karsten Suhre, Gabi Kastenmüller, Susan J Sumner, Ines Thiele, Oliver Fiehn, Rima Kaddurah-Daouk
INTRODUCTION BACKGROUND TO METABOLOMICS: Metabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or "-omics" level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person's metabolic state provides a close representation of that individual's overall health status...
2016: Metabolomics: Official Journal of the Metabolomic Society
Steve M Harakeh, Imran Khan, Taha Kumosani, Elie Barbour, Saad B Almasaudi, Suhad M Bahijri, Sulaiman M Alfadul, Ghada M A Ajabnoor, Esam I Azhar
Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD...
2016: Frontiers in Cellular and Infection Microbiology
Silvia Turroni, Jessica Fiori, Simone Rampelli, Stephanie L Schnorr, Clarissa Consolandi, Monica Barone, Elena Biagi, Flaminia Fanelli, Marco Mezzullo, Alyssa N Crittenden, Amanda G Henry, Patrizia Brigidi, Marco Candela
The recent characterization of the gut microbiome of traditional rural and foraging societies allowed us to appreciate the essential co-adaptive role of the microbiome in complementing our physiology, opening up significant questions on how the microbiota changes that have occurred in industrialized urban populations may have altered the microbiota-host co-metabolic network, contributing to the growing list of Western diseases. Here, we applied a targeted metabolomics approach to profile the fecal metabolome of the Hadza of Tanzania, one of the world's few remaining foraging populations, and compared them to the profiles of urban living Italians, as representative of people in the post-industrialized West...
2016: Scientific Reports
Giovanni Barbara, Eleonora Scaioli, Maria Raffaella Barbaro, Elena Biagi, Luca Laghi, Cesare Cremon, Giovanni Marasco, Antonio Colecchia, Gianfranco Picone, Nunzio Salfi, Francesco Capozzi, Patrizia Brigidi, Davide Festi
OBJECTIVE: The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study. DESIGN: Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls...
September 12, 2016: Gut
Kei E Fujimura, Alexandra R Sitarik, Suzanne Havstad, Din L Lin, Sophia Levan, Douglas Fadrosh, Ariane R Panzer, Brandon LaMere, Elze Rackaityte, Nicholas W Lukacs, Ganesa Wegienka, Homer A Boushey, Dennis R Ownby, Edward M Zoratti, Albert M Levin, Christine C Johnson, Susan V Lynch
Gut microbiota bacterial depletions and altered metabolic activity at 3 months are implicated in childhood atopy and asthma. We hypothesized that compositionally distinct human neonatal gut microbiota (NGM) exist, and are differentially related to relative risk (RR) of childhood atopy and asthma. Using stool samples (n = 298; aged 1-11 months) from a US birth cohort and 16S rRNA sequencing, neonates (median age, 35 d) were divisible into three microbiota composition states (NGM1-3). Each incurred a substantially different RR for multisensitized atopy at age 2 years and doctor-diagnosed asthma at age 4 years...
October 2016: Nature Medicine
Maria Elizabeth de Sousa Rodrigues, Mandakh Bekhbat, Madelyn C Houser, Jianjun Chang, Douglas I Walker, Dean P Jones, Claudia M P Oller do Nascimento, Christopher J Barnum, Malú G Tansey
The mechanisms underlying the association between chronic psychological stress, development of metabolic syndrome (MetS), and behavioral impairment in obesity are poorly understood. The aim of the present study was to assess the effects of mild chronic psychological stress on metabolic, inflammatory, and behavioral profiles in a mouse model of diet-induced obesity. We hypothesized that (1) high-fat high-fructose diet (HFHF) and psychological stress would synergize to mediate the impact of inflammation on the central nervous system in the presence of behavioral dysfunction, and that (2) HFHF and stress interactions would impact insulin and lipid metabolism...
September 1, 2016: Brain, Behavior, and Immunity
Guangmang Liu, Xianjian Wu, Gang Jia, Xiaoling Chen, Hua Zhao, Jing Wang, Caimei Wu, Jingyi Cai
Arginine regulates growth performance, nutrient metabolism and health effects, but the underlying mechanism remains unknown. This study aims to investigate the effect of dietary arginine supplementation on rat growth performance and urinary metabolome through ¹H-NMR spectroscopy. Twenty rats were randomly assigned to two groups supplemented with 0% or 1.0% l-arginine for 4 weeks. Urine samples were analyzed through NMR-based metabolomics. Arginine supplementation significantly increased the urine levels of 4-aminohippurate, acetate, creatine, creatinine, ethanolamine, formate, hippurate, homogentisate, indoxyl sulfate, and phenylacetyglycine...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Matthew W Ralls, Farokh Rustom Demehri, Yongjia Feng, Sasha Raskind, Chunhai Ruan, Arno Schintlmeister, Alexander Loy, Buck Hanson, David Berry, Charles F Burant, Daniel H Teitelbaum
BACKGROUND: Total parenteral nutrition (TPN) leads to a shift in small intestinal microbiota with a characteristic dominance of Proteobacteria. This study examined how metabolomic changes within the small bowel support an altered microbial community in enterally deprived mice. METHODS: C57BL/6 mice were given TPN or enteral chow. Metabolomic analysis of jejunal contents was performed by liquid chromatography/mass spectrometry (LC/MS). In some experiments, leucine in TPN was partly substituted with (13)C-leucine...
September 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Henrik M Roager, Lea B S Hansen, Martin I Bahl, Henrik L Frandsen, Vera Carvalho, Rikke J Gøbel, Marlene D Dalgaard, Damian R Plichta, Morten H Sparholt, Henrik Vestergaard, Torben Hansen, Thomas Sicheritz-Pontén, H Bjørn Nielsen, Oluf Pedersen, Lotte Lauritzen, Mette Kristensen, Ramneek Gupta, Tine R Licht
Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites...
2016: Nature Microbiology
Erikka Loftfield, Emily Vogtmann, Joshua N Sampson, Steven C Moore, Heidi Nelson, Rob Knight, Nicholas Chia, Rashmi Sinha
BACKGROUND: The gut metabolome may be associated with the incidence and progression of numerous diseases. The composition of the gut metabolome can be captured by measuring metabolite levels in the feces. However, there are little data describing the effect of fecal sample collection methods on metabolomic measures. METHODS: We collected fecal samples from 18 volunteers using four methods: no solution, 95% ethanol, fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT)...
August 19, 2016: Cancer Epidemiology, Biomarkers & Prevention
Guangmang Liu, Wei Cao, Tingting Fang, Gang Jia, Hua Zhao, Xiaoling Chen, Caimei Wu, Jing Wang
Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution ¹H NMR metabolic profiling combined with multivariate data analysis...
2016: Nutrients
Maryam Goudarzi, Tytus D Mak, Jonathan P Jacobs, Bo-Hyun Moon, Steven J Strawn, Jonathan Braun, David J Brenner, Albert J Fornace, Heng-Hong Li
Medical responders to radiological and nuclear disasters currently lack sufficient high-throughput and minimally invasive biodosimetry tools to assess exposure and injury in the affected populations. For this reason, we have focused on developing robust radiation exposure biomarkers in easily accessible biofluids such as urine, serum and feces. While we have previously reported on urine and serum biomarkers, here we assessed perturbations in the fecal metabolome resulting from exposure to external X radiation in vivo...
September 2016: Radiation Research
V Marrachelli, D Monleon, J M Morales, F Martínez, J C Martin-Escudero, J Redon
OBJECTIVE: We aimed to screen metabolomes of combined hypertension and obesity in a Spanish general population cohort to identify differential metabolic profiles for better risk estimation and patient stratification. DESIGN AND METHOD: We measured blood serum high resolution NMR spectra from hypertensive subjects with (HT_OB, n = 356) or without (HT_noOB, n = 280) abdominal obesity and normotensive subjects with (noHT_OB, n = 291) or without (noHT_noOB, n = 555) abdominal obesity for detecting metabolic cores specifically affected in the different groups...
September 2016: Journal of Hypertension
Pamela Vernocchi, Federica Del Chierico, Lorenza Putignani
The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases...
2016: Frontiers in Microbiology
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